INHIBITORS OF CHOLESTEROL-BIOSYNTHESIS .2. 1,3,5-TRISUBSTITUTED [2-(TETRAHYDRO-4-HYDROXY-2-OXOPYRAN-6-YL)ETHYL]PYRAZOLES

A series of 1,3,5-trisubstituted pyrazole mevalonolactones were prepared and evaluated for their ability to inhibit the enzyme HMG-CoA reductase in vitro. Since previous studies suggested that the 5-(4-fluorophenyl) and 3-(l-methylethyl) substituents afforded optimum potency, attention was focused on variations in position 1 of the pyrazole ring. Biological evaluation of analogues bearing a variety of 1-substituents suggested that, although most substituents were tolerated, none afforded an advantage over phenyl, which exhibited potency comparable to that of compactin in vitro. © 1990, American Chemical Society. All rights reserved.